| Objective: To observe the curative effect of sequential therapy on liver VX2 tumor in rabbits by using CRFA combined with heat-ADM-lipiodol via hepatic artery, and to evaluate its validity, safe and utility.Methods:48 rabbit models with implanted VX2 tumors were used for this study.24 rabbits out of them were treated with hepatic artery catheterization on the third weekend after they were implanted VX2 tumors, then they were randomly divided into 2 groups, a heat-ADM-lipiodol group (n=12), a combination group(n=12); the other 24 rabbits were also randomly divided into 2 groups, a control group(n=12), a CRFA group(n=12). ALT was detected pretherapy and on the day 3,7 post-treatment. The longest and shortest diameter of VX2 tumor in rabbit liver were measured by ultrasound pretherapy and on the second weekend post-treatment. The gross tumor volume, the tumor growth rate and the inhibition ratio of gross tumor volume were calculated. All of the rabbits were killed, then the metastasis status in liver and to lung or lymphoid node was recorded carefully 14 days post-treatment. Pathology change was observed by HE staining, ultrastructure was observed by TEM. The expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) were examined by immunohistochemistry. The tumor cell apoptosis was detected by TUNEL.Results:1. Gross tumor volume in each group showed no significant difference pretherapy(P﹥0.05).Tumor growth rate in control group was (328±84)% and higher than those in every therapy group apparently(P﹤0.01). Tumor growth rate in combination group was (116±17)% and lower than those in solitary therapy group apparently(P﹤0.05). The inhibition ratio of gross tumor volume in combination group was 65.38% and higher than those in another 2 therapy groups.2. ALT of all the rabbits in each group showed no significant difference pretherapy(P﹥0.05). ALT in each group increased transiently post-treatment. On the seventh day, ALT in 2 solitary therapy groups descended to normal level, and ALT in combination group was a little higher than it in control group. This might be concerned to detecting in short time.3. Pathology observation: In control group, tumor showed expansive growth without visible membrane, cell nucleus was big and deep staining , abnormal division could be seen frequently. There was much coagulative necrosis of central tumor tissue in CRFA group and combination group. After therapeutic alliance ,there was inflammatory reaction zone in the peripheric tissue. After CRFA, we could see reliquus tumor cells infrequently in the peripheric tissue. In heat-ADM-lipiodol group, the amount of tumor cells decreased apparently, and reliquus tumor cells are surrounded by fibrous tissue to shape cancer nest or trabeculum structure.4.TEM observation: In control group, tumor cell's contour was complete, cell-cell contact was compact, elliptic mitochondria showed elliptic and cell nucleus was big, chromatin distributed uniformly. In combination group, necrosis of tumor cells such as nuclear fragmentation and caryolysis was apparent in the central tissue, and we could see many apoptotic bodies or apoptotic cells in the peripheric tissue.5.The apoptotic index of tumor cell: control group(17.8±7.05)%, CRFA group(35.4±8.29)%, heat-ADM-lipiodol group(42.7±6.53)%, combination group(54.1±8.74)%. The apoptotic index in combination group was significantly higher than control group and another 2 therapy groups(P﹤0.05). There was negative correlation between apoptotic index and gross tumor volume in combination group(r=-0.585,P﹤0.05).6.The expression of VEGF in combination group was the lowest of 4 groups, its positive rate was 41.7%. The expression of VEGF showed significant differences between combination group and control group or heat-ADM-lipiodol group(P﹤0.05). The expression of VEGF showed no significant difference between combination group and CRFA group(P﹥0.05). The expression positive rate of bFGF in combination group was 25%, and it's lower than those in control group or heat-ADM-lipiodol group(P﹤0.05). The expression positive rate of bFGF in combination group was slightly higher than that in CRFA group, and there was no significant difference between them(P﹥0.05).The metastasis rate of tumor in combination group was 33.3% and significantly lower than control group's 91.7%(P<0.01). The metastasis rate of tumor showed no significant differences between combination group and another 2 therapy groups(P﹥0.05).Conclusions: Sequential therapy on liver VX2 tumor in rabbits by using CRFA combined with heat-ADM-lipiodol via hepatic artery could prevent tumor tissue from growing up apparently. Combining therapy was safe with transient injury to the liver function of the rabbits. This experiment had the merit of CRFA that could kill tumor cells in treatment region thoroughly, and the merit of heat-ADM-lipiodol that could decrease blood supply of tumor and increase the therapeutic effect of chemotherapeutics. Combining therapy could enhance the necrosis and apoptosis of tumor cell. Combining therapy could cut down the expression of angiogenesis factor after heat-ADM-lipiodol therapy. It's an effective sequential therapy to treat liver neoplasms, and it had the value of clinical application to some extent with better therapeutic effect than solitary therapy. |
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